Argininosuccinate synthase 1 and periportal gene expression in sonic hedgehog hepatocellular adenomas

Jean‐Charles Nault, Gabrielle Couchy, Stefano Caruso, Léa Meunier, Laure Caruana, Eric Letouzé, Sandra Rebouissou, Valérie Paradis, Julien Calderaro, Jessica Zucman‐Rossi – 24 March 2018 – Genetic alterations define different molecular subclasses of hepatocellular adenoma (HCA) linked with risk factors, histology and clinical behavior. Recently, Argininosuccinate Synthase 1 (ASS1), a major periportal protein, was proposed as a marker of HCA with a high risk of hemorrhage. We aimed to assess the significance of ASS1 expression through the scope of the HCA molecular classification.

Nicotinamide adenine dinucleotide phosphate (reduced) oxidase 2 modulates inflammatory vigor during nonalcoholic fatty liver disease progression in mice

Rajib Mukherjee, Maria E. Moreno‐Fernandez, Daniel A. Giles, Monica Cappelletti, Traci E. Stankiewicz, Calvin C. Chan, Senad Divanovic – 24 March 2018 – Nonalcoholic fatty liver disease (NAFLD) represents a disease spectrum ranging from benign steatosis to life‐threatening cirrhosis and hepatocellular carcinoma. Elevated levels of reactive oxygen species (ROS) and exacerbated inflammatory responses have been implicated in NAFLD progression.

Na+‐taurocholate cotransporting polypeptide inhibition has hepatoprotective effects in cholestasis in mice

Davor Slijepcevic, Reinout L.P. Roscam Abbing, Claudia D. Fuchs, Lizette C.M. Haazen, Ulrich Beuers, Michael Trauner, Ronald P.J. Oude Elferink, Stan F.J. van de Graaf – 24 March 2018 – Accumulation of bile salts (BSs) during cholestasis leads to hepatic and biliary injury, driving inflammatory and fibrotic processes. The Na+‐Taurocholate Cotransporting Polypeptide (NTCP) is the major hepatic uptake transporter of BSs, and can be specifically inhibited by myrcludex B. We hypothesized that inhibition of NTCP dampens cholestatic liver injury.

Ubiquitin‐Specific Protease 4 Is an Endogenous Negative Regulator of Metabolic Dysfunctions in Nonalcoholic Fatty Liver Disease in Mice

Yichao Zhao, Fang Wang, Lingchen Gao, Longwei Xu, Renyang Tong, Nan Lin, Yuanyuan Su, Yang Yan, Yu Gao, Jie He, Lingcong Kong, Ancai Yuan, Ying Zhuge, Jun Pu – 23 March 2018 – Nonalcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis (HS), insulin resistance (IR), and inflammation, poses a high risk of cardiometabolic disorders. Ubiquitin specific protease 4 (USP4), a deubiquitinating enzyme, is pivotally involved in regulating multiple inflammatory pathways; however, the role of USP4 in NAFLD is unknown.

NI‐0801, an anti‐chemokine (C‐X‐C motif) ligand 10 antibody, in patients with primary biliary cholangitis and an incomplete response to ursodeoxycholic acid

Kathy L. de Graaf, Geneviève Lapeyre, Florence Guilhot, Walter Ferlin, Stuart M. Curbishley, Marco Carbone, Paul Richardson, Sulleman Moreea, C. Anne McCune, Stephen D. Ryder, Roger W. Chapman, Annarosa Floreani, David E. Jones, Cristina de Min, David H. Adams, Pietro Invernizzi – 23 March 2018 – NI‐0801 is a fully human monoclonal antibody against chemokine (C‐X‐C motif) ligand 10 (CXCL10), which is involved in the recruitment of inflammatory T cells into the liver. The safety and efficacy of NI‐0801 was assessed in patients with primary biliary cholangitis.

A real‐world observational cohort of patients with primary biliary cholangitis: TARGET‐primary biliary cholangitis study design and rationale

Cynthia Levy, Christopher L. Bowlus, Elizabeth Carey, Julie M. Crawford, Karen Deane, Marlyn J. Mayo, W. Ray Kim, Michael W. Fried – 23 March 2018 – Primary biliary cholangitis (PBC) is a rare chronic cholestatic liver disease that may progress to biliary cirrhosis if left untreated. The first‐line therapy for PBC is ursodeoxycholic acid (UDCA). Unfortunately, 1 of 3 patients does not respond to UDCA. These patients are at risk for developing clinical events, including cirrhosis, complications of portal hypertension, hepatocellular carcinoma, liver transplant, or death. Recently, the U.S.

Propensity‐Matched Analysis of Patients with Mixed Hepatocellular‐Cholangiocarcinoma and Hepatocellular Carcinoma Undergoing Liver Transplantation

Keri E. Lunsford, Colin Court, Yong Seok Lee, David S. Lu, Bita V. Naini, Michael P. Harlander‐Locke, Ronald W. Busuttil, Vatche G. Agopian – 23 March 2018 – Mixed hepatocellular‐cholangiocarcinomas (HCC‐CCAs) are rare tumors with both hepatocellular and biliary differentiation. While liver transplantation (LT) is the gold standard treatment for patients with unresectable hepatocellular carcinoma (HCC), it is contraindicated in known HCC‐CCA because of concerns of poor prognosis. We sought to compare posttransplant oncologic outcomes for HCC‐CCA and a matched cohort of HCC LT recipients.

Acute hepatitis B virus infection in humanized chimeric mice has multiphasic viral kinetics

Yuji Ishida, Tje Lin Chung, Michio Imamura, Nobuhiko Hiraga, Suranjana Sen, Hiroshi Yokomichi, Chise Tateno, Laetitia Canini, Alan S. Perelson, Susan L. Uprichard, Harel Dahari, Kazuaki Chayama – 23 March 2018 – Chimeric urokinase type plasminogen activator (uPA)/severely severe combined immunodeficiency (SCID) mice reconstituted with humanized livers are useful for studying hepatitis B virus (HBV) infection in the absence of an adaptive immune response.

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